Identification of a novel apoptosis-inducing factor derived from leukemic cells: endothelial interleukin-8, but not monocyte-derived, induces apoptosis in leukemic cells.
The human myelogenous leukemia cell line HL-60, treated with phorbol 12, 13-dibutyrate (PDBu), produces apoptosis-inducing factors (AIFs) in leukemic cells. We have purified AIF against leukemic cell line K562 as target cells, and N-terminal amino acid sequencing analysis revealed that this purified protein is identical to endothelial cell-derived interleukin-8 ([(Ala)-IL-8]77). In Western blot analysis of supernatants of PDBu-treated HL-60 cells, only [(Ala)-IL-8]77 was detected. Moreover, recombinant human [(Ala)-IL-8]77 induced apoptosis in leukemic cell lines such as K562, HL-60, KG-1, U937, THP-1 and Jurkat, but monocyte-derived IL-8 ([(Ser)-IL-8]72) did not. Therefore [(Ala)-IL-8]77 plays an important role in inducing apoptosis against leukemic cells and may lead to a new therapy for leukemia.
Terui
Y
Y
Department of Internal Medicine, Jichi Medical School, Tochigi, Japan.
Ikeda
M
M
Tomizuka
H
H
Kasahara
T
T
Ohtsuki
T
T
Uwai
M
M
Mori
M
M
Itoh
T
T
Tanaka
M
M
Yamada
M
M
Shimamura
S
S
Miura
Y
Y
Hatake
K
K
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018922:HL-60 Cells / Q000737:chemistry*; D006801:Humans; D016209:Interleukin-8 / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000302:isolation & purification* / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D017421:Sequence Analysis; D014407:Tumor Cells, Cultured
D016209:Interleukin-8; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C070593:interleukin 8 (77), Ala-; D015240:Phorbol 12,13-Dibutyrate